Unlock instant, AI-driven research and patent intelligence for your innovation.

Anti-TIGIT antibody pharmaceutical composition and application thereof

A composition and drug technology, applied in the direction of drug combination, antibody, drug delivery, etc., can solve problems such as TIGIT antibody application

Active Publication Date: 2020-10-09
JIANGSU HENGRUI MEDICINE CO LTD +1
View PDF14 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, no TIGIT antibody has been used clinically

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Anti-TIGIT antibody pharmaceutical composition and application thereof
  • Anti-TIGIT antibody pharmaceutical composition and application thereof
  • Anti-TIGIT antibody pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0175] Embodiment 1, the preparation of anti-TIGIT antibody

[0176] 1. Preparation of Antigen and Antibody

[0177] 1.1 Protein design and expression

[0178] Using human TIGIT protein (Uniprot number: Q495A1) as the template of TIGIT of the present disclosure, design the amino acid sequence of the antigen and detection protein of the present disclosure, optionally fuse different tags on the basis of TIGIT protein, and clone them respectively on the pHr vector ( Self-produced) or pXC-17.4 vector (LONZA), transiently expressed in 293 cells or stably expressed and purified in CHO cells, to obtain the protein encoding the disclosed antigen and detection. The following TIGIT antigens refer to human TIGIT unless otherwise specified.

[0179] Fusion protein of TIGIT extracellular region and mouse IgG2aFc fragment: TIGIT-mFc, for immunization and detection

[0180]

[0181]

[0182] Note: The underlined part is the signal peptide, and the italic part is mFc.

[0183] Fusio...

Embodiment 2

[0435] Embodiment 2, anti-TIGIT antibody activity test experiment

[0436] One: ELISA experiment of TIGIT antibody binding to human TIGIT protein

[0437]The binding ability of the anti-TIGIT antibody was detected by ELISA experiment between the antibody and human TIGIT protein. The TIGIT fusion protein with Fc or mFc tag is immobilized in a 96-well microtiter plate by binding to the anti-Fc or mFc antibody coated in the microtiter plate, and the strength of the signal after the antibody is added is used to judge the antibody and TIGIT The positive control molecules are 22G2-H3Q and 10A7 hIgG4 (wherein the light and heavy chain variable region sequence of 10A7 hIgG4 is from SEQ ID NO: 21 and 22 in US20130251720A1, and its light and heavy chain variable region is connected to form the light and heavy chain of the full-length antibody The constant regions are respectively SEQ ID NO: 79 and 78 of the present application) The specific experimental method is as follows:

[0438] ...

Embodiment 3

[0490] The mensuration of embodiment 3.TIGIT antibody Tm value

[0491] Prepare 10mM disodium hydrogen phosphate-citric acid (PB-CA) buffer solutions with different pH values ​​(see 1) to 6) below), and prepare antibody preparations with an anti-TIGIT antibody concentration of 1 mg / ml:

[0492] 1) 10mM disodium hydrogen phosphate-citric acid, pH4.5

[0493] 2) 10mM disodium hydrogen phosphate-citric acid, pH5.0

[0494] 3) 10mM disodium hydrogen phosphate-citric acid, pH5.5

[0495] 4) 10mM disodium hydrogen phosphate-citric acid, pH6.0

[0496] 5) 10mM disodium hydrogen phosphate-citric acid, pH6.5

[0497] 6) 10mM disodium hydrogen phosphate-citric acid, pH7.0

[0498]The thermal stability of anti-TIGIT antibody in each group of preparations was determined by differential scanning calorimetry (DSC). The test results are shown in Table 20, and the results show that the anti-TIGIT antibody is relatively stable at pH 5.0-7.0.

[0499] Table 20. Tm values ​​of different pH...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
concentrationaaaaaaaaaa
Login to View More

Abstract

The present disclosure relates to an anti-TIGIT antibody pharmaceutical composition and an application thereof. Specifically, the present disclosure relates to a pharmaceutical composition comprisingan anti-TIGIT antibody or an antigen-binding fragment thereof and a buffer solotion. Further, the pharmaceutical composition further comprises a sugar and a surfactant. The pharmaceutical compositionsof the present disclosure are useful in the treatment of T cell dysfunction disorders.

Description

technical field [0001] The present disclosure relates to methods and drug combinations for treating diseases with anti-TIGIT antibodies combined with PD-1 inhibitors. Background technique [0002] The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art. [0003] In recent years, immune checkpoint therapy targeting immune cell co-inhibitory receptors has made great progress in tumor immunotherapy, and the discovery and verification of new co-inhibitory receptors has become a global competitive hotspot. T cells are the key mediators of the immune response, and the activation of T cells depends on TCR signaling and co-stimulatory signals. Co-stimulatory signals are limiting signals for T cell activation, and their dysfunction is involved in the occurrence of autoimmune diseases (Immunol Rev, 2012, 248:122-139; AutoimmunRev, 2013, 12: 1171-1176). TIGIT (T cell immunoglobulin and ITIM domain) is ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K9/08A61K9/19A61K47/18A61K47/12A61K47/26A61P35/00A61P35/02
CPCC07K16/2803A61K9/19A61K9/08A61K47/183A61K47/12A61K47/26A61P35/00A61P35/02A61K2039/505C07K2317/24C07K2317/622Y02A50/30
Inventor 杨健健李皓刘洵付雅媛
Owner JIANGSU HENGRUI MEDICINE CO LTD